Micromarrows—Three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells

Cook, Matthew M., Futrega, Kathryn, Osiecki, Michael, Kabiri, Mahboubeh, Kul, Betul, Rice, Alison, Atkinson, Kerry, Brooke, Gary, & Doran, Michael (2012) Micromarrows—Three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells. Tissue Engineering Part C: Methods, 18(5), pp. 319-328.

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Hematopoietic stem cell (HSC) transplant is a well established curative therapy for some hematological malignancies. However, achieving adequate supply of HSC from some donor tissues can limit both its application and ultimate efficacy. The theory that this limitation could be overcome by expanding the HSC population before transplantation has motivated numerous laboratories to develop ex vivo expansion processes. Pioneering work in this field utilized stromal cells as support cells in cocultures with HSC to mimic the HSC niche. We hypothesized that through translation of this classic coculture system to a three-dimensional (3D) structure we could better replicate the niche environment and in turn enhance HSC expansion. Herein we describe a novel high-throughput 3D coculture system where murine-derived HSC can be cocultured with mesenchymal stem/stromal cells (MSC) in 3D microaggregates—which we term “micromarrows.” Micromarrows were formed using surface modified microwells and their ability to support HSC expansion was compared to classic two-dimensional (2D) cocultures. While both 2D and 3D systems provide only a modest total cell expansion in the minimally supplemented medium, the micromarrow system supported the expansion of approximately twice as many HSC candidates as the 2D controls. Histology revealed that at day 7, the majority of bound hematopoietic cells reside in the outer layers of the aggregate. Quantitative polymerase chain reaction demonstrates that MSC maintained in 3D aggregates express significantly higher levels of key hematopoietic niche factors relative to their 2D equivalents. Thus, we propose that the micromarrow platform represents a promising first step toward a high-throughput HSC 3D coculture system that may enable in vitro HSC niche recapitulation and subsequent extensive in vitro HSC self-renewal.

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ID Code: 55609
Item Type: Journal Article
Refereed: Yes
Keywords: Hematopoietic stem cells, mesenchymal stem/ stromal cells, co-culture, bioreactor, transplant
DOI: 10.1089/ten.tec.2011.0159
ISSN: 1937-3392
Subjects: Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomedical Engineering not elsewhere classified (090399)
Australian and New Zealand Standard Research Classification > TECHNOLOGY (100000) > MEDICAL BIOTECHNOLOGY (100400) > Regenerative Medicine (incl. Stem Cells and Tissue Engineering) (100404)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 Mary Ann Liebert, Inc.
Copyright Statement: This is a copy of an article published in Tissue Engineering Part C: Methods [copyright Mary Ann Liebert, Inc.]; Tissue Engineering Part C: Methods is available online at: http://online.liebertpub.com.
Deposited On: 14 Dec 2012 04:12
Last Modified: 18 Dec 2012 04:07

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